摘要
目的 构建灵敏、快捷、稳定的拉莫三嗪(LTG)血药浓度高效液相色谱(HPLC)测定法,并对其常见影响因素进行分析.方法 用Agilent Exlipse XDB-C18(4.6×150mm,5μm)色谱柱,柱温25℃;以40mM/L甲酸铵-乙腈-0.25%三乙胺(70:20:10,V/V)为流动相,流速1ml/min;用310nm波长检测LTG,250nm波长检测内标(非那西丁);比较同血样中血浆和全血LTG浓度的差异性;将其他常见抗癫痫药物加入待测LTG血样中观察是否对LTG测定产生干扰.结果 LTG在0.1~50μg/ml范围内线性良好(r>0.999),定量下限为0.1μg/ml,提取回收率为75.67%~83.12%,日内日间精密度、进样瓶内、冷藏及冻融稳定性RSD均<10%,同血样中血浆和全血LTG浓度差异无统计学意义(双侧t=3.880,P=0.001).结论 LTG血浆药物浓度HPLC检测法稳定性好、灵敏度高、且不受其他常见抗癫痫药物干扰,可用于临床治疗药物浓度检测.且临床取血量少或血样溶血时可以使用全血代替血浆进行LTG浓度测定.
Objective To develop a quick,stable and fully validated HPLC method for determination of lamotrigine(LTG)in human plasma for therapy drug monitor, and to study its common factors. Methods Chromatographic separation was performed on a Agilent Exlipse XDB-C18 column (4.6×150mm,5μm),and the column temperature was 25℃. The mobile phase consisted of 40 mM/L ammonium formate-acetonitrile-0.25% triethylamine(70:20:10,V/V),and the velocity of flow was 1ml/min. The wave length of detection was 310 nm for LTG,and 250 nm for the internal standard(Phenacetin). Making two tails paired t-test between LTG concentrations in plasma and in whole blood of the same sample in order to study whether there were differences. The others common anti-epileptic drugs were added to the blood sample to test whether they will interfer the determination of LTG. Results A linear response function was established for the range of concentrations 0.1~50μg/ml(r>0.999)for LTG. The lowest limit of quantification was 0.1μg/ml. The recoveries of this method were 75.67%~83.12% for LTG.The intra-day and inter-day precision values (RSD) was less than 10%.After being stored in sample bottle,frozen and freeze-thaw it stability RSD were less than 10%. There were no significant difference of LTG concentrations in blood plasma and whole blood for the same sample(two tails t=3.880,P=0.001). Conclusion LTG plasma drug concentration determination by high performance liquid chromatography has good stability, high sensitivity, and is not interfered by other common anti-epileptic drugs. It can be used for clinical drug concentration detection. Whole blood can be used instead of plasma to determine LTG concentration when blood sample is less or hemolysis occurs.
出处
《浙江临床医学》
2019年第3期299-301,共3页
Zhejiang Clinical Medical Journal
